Our interdisciplinary team (with special expertise in hepatology, gastroenterology, pathology, biochemistry, nutrition, immunology, community medicine and endocrinology) will continue studies in patients as well as in our experimental models of alcoholic injury in the rat and the baboon in which liver lesions seen in the alcoholic, including cirrhosis were reproduced. We plan to pursue our studies of the biochemical differences between alcoholics and nonalcoholics, including alterations of alcohol metabolism that may help elucidate the biochemical basis for the metabolic tolerance to ethanol. Abnormalities in intermediary and protein metabolism will be delineated. The role of protein retention and immunological reactions in the development of alcoholic liver diseases will be determined. The nature of alcohol related abnormalities in collagen metabolism relevant to the pathogenesis of cirrhosis will be studied. We will try to identify factors predisposing to cirrhosis and characterize stages intermediate between fatty liver and cirrhosis. Pathogenesis of alcohol induced intestinal lesions will be assessed, including the potential carcinogenic role of alcohol and the mechanism of the alcohol induced diarrhea. The pathogenesis of zinc deficiency in the alcoholic and its implication for hepatic and hematologic disorders will be studied. Interaction of alcohol and liver disease with thiamine metabolism will be evaluated including the possible consequences on the central nervous system. Disorders of vitamin A metabolism and associated endocrine consequences will be studied. Abnormalities in muscle will be assessed with regard to mitochondrial functions, contractile proteins and amino acid metabolism. Alterations in plasma amino acids will also be used to evaluate the prevalence of alcoholism in a group of employees and possible beneficial effects of early detection. Whenever possible, our baboon model will be made available as a resource to other interested investigators. Our ultimate goal is the application of the newly acquired knowledge to the successful prevention and treatment of alcohol related diseases through exhaustive investigation of our experimental models and judicious verification of key findings in carefully controlled clinical studies.